(NEW YORK) -- Two Republican challengers, Rep. Julia Letlow and state Treasurer John Fleming, will advance to a runoff election in Louisiana's closely watched GOP primary, The Associated Press projected Saturday -- a defeat for Sen. Bill Cassidy who had drawn the ire of President Donald Trump.
Letlow had been endorsed by Trump in a three-way race that was seen as a test of the president's influence among Republicans.
Letlow and Fleming will face off again in the runoff on June 27.
With nearly 100% of the estimated vote counted, Letlow led with about 45% of the vote, followed by Fleming with about 28%, according to the AP. Cassidy trailed with about 25% of the vote.
The primary defeat marks a stunning loss for Cassidy and a potential warning to other Republicans who risk defying the president, as Trump has sought to oust those he views as disloyal. Trump-backed candidates recently defeated several Indiana state senators who opposed his redistricting plans.
Cassidy's defeat makes him the first sitting senator to lose a primary since 2017 and the first elected incumbent senator to lose a primary since 2012 -- when Indiana GOP Sen. Richard Lugar lost his race to a Tea Party challenger.
Cassidy expressed gratitude for his time in office and acknowledged the race didn't go like he would have liked.
"But you don't pout, you don't whine, you don't claim the election was stolen," he said. "You don't manufacture some excuse --you thank the voters for the privilege of representing the state or the country for as long as you've had that privilege, and that's what I'm doing right now."
He also took a thinly veiled jab at Trump without naming him.
"Our country is not about one individual, it is about the welfare of all Americans, and it is about our Constitution," he said. "And it is the welfare of my people and my state and my country and our Constitution, to which I am loyal."
Trump celebrates
In a post on his social media platform, Trump celebrated Cassidy's projected defeat and congratulated Letlow.
"Julia Letlow is a fantastic person and, after taking care of some additional business, will make a brilliant Senator for the Great People of Louisiana," Trump said in the post.
In speech to supporters in Baton Rouge on Saturday night, Letlow opened her remarks thanking Trump.
"I want to say thank you to a very special man, who you all know – the best president this country has ever had: President Donald Trump," Letlow said.
"When he endorsed me in January, I knew this was going to be a tough race, but tonight Louisiana sent a clear message -- that they want a candidate to represent them in the Senate who will always put America first and never turn her back on Louisiana voters," Letlow continued.
Fleming expressed full confidence he will win the runoff.
"I embrace this challenge enthusiastically. The runoff starts today, and I could not be more energized," he said in a statement on Sunday.
"The people of Louisiana deserve a senator who cannot be bought, will not be bossed, and will never back down," Fleming said.
On the campaign trail
On the campaign trail, Letlow, a three-term congresswoman, was anything but shy about Trump's endorsement, casting Cassidy as disloyal and Fleming as out of touch with the president. Her campaign messaging focused in part on defending parental rights and securing the border.
Fleming, a former congressman who later served in various roles in the first Trump administration, pitched himself to voters as the most staunch conservative, though he did not receive a public endorsement from Trump.
For his part, Cassidy, a physician who was first elected to the Senate seat in 2014, argued his record proved he delivered for Louisianans and sought to tie himself to Trump -- campaigning on a conservative agenda, arguing against abortion, supporting "strong borders" and co-sponsoring the SAVE America Act, a legislative priority for Trump.
Trump's endorsement
Trump upended Cassidy's reelection bid in January when he encouraged Letlow to enter in hopes of defeating Cassidy.
Trump sought to punish Cassidy, who broke with the party as one of seven senators to vote to convict Trump for his role in inciting the Jan. 6 Capitol riot. The 57-43 vote fell shy of the 67 vote threshold needed to convict Trump.
In a Saturday morning social media post -- roughly two hours after polls opened --Trump again ripped on the two-term incumbent while endorsing Letlow. He called Cassidy "disloyal" and castigated him for using his name throughout the campaign.
Despite their fraught relationship, Cassidy has, at times, supported Trump's agenda. Cassidy, a physician and longtime proponent of vaccines, grilled Health Secretary Robert F. Kennedy Jr. -- a vaccine skeptic -- during his confirmation hearing but cast the deciding vote to advance his nomination.
Yet for some, Cassidy's vote to convict Trump may have been enough to do him in.
Robert Hogan, a political science professor at Louisiana State University, told ABC News ahead of the primary that some voters still had a "visceral" reaction to Cassidy's vote to convict the president.
"The Republican activists have been unforgiving," Hogan said. "This says less about Cassidy, I would say, than it says about the nature of the attraction that voters have towards Trump."